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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Endovascular treatment (EVT) is the main treatment for peripheral artery disease (PAD). Despite advances in device development, the restenosis rate remains high in patients with femoropopliteal lesions (FP). This study aimed to evaluate the effectiveness of exercise training in reducing the 1-year in-stent restenosis rate of bare metal nitinol stents for FPs. This prospective, randomized, open-label, multicenter study was conducted from January 2017 to March 2019. We randomized 44 patients who had claudication with de novo stenosis or occlusion of the FP into an intensive exercise group (n = 22) and non-intensive exercise group (n = 22). Non-intensive exercise was defined as walking for less than 30 min per session, fewer than three times a week. We assessed exercise tolerance using an activity meter at 1, 3, 6, and 12 months, and physiotherapists ensured maintenance of exercise quality every month. The primary endpoint was instant restenosis defined as a peak systolic velocity ratio > 2.5 on duplex ultrasound imaging. Kaplan–Meier analysis was used to evaluate the data. There were no significant differences in background characteristics between the groups. Six patients dropped out of the study within 1 year. In terms of the primary endpoint, intensive exercise significantly improved the patency rate of bare nitinol stents at 12 months. The 1-year freedom from in-stent restenosis rates were 81.3% in the intensive exercise group and 47.6% in the non-intensive exercise group (p = 0.043). No cases of stent fracture were observed in the intensive exercise group. Intensive exercise is safe and reduces in-stent restenosis in FP lesions after endovascular therapy for PAD. Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry (No. UMIN 000025259).

Background: During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however. Methods: We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant. Results: We found that cardiac expression of Gα o , an inhibitory G protein encoded in humans by GNAO1 , is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of Gnao1 ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of GNAO1 in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gα o expression increased surface sarcolemmal L-type Ca 2+ channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca 2+ handling in ventricular myocytes, which led to cardiac dysfunction. Conclusions: These findings shed light on a novel function of Gα o in the regulation of cardiac Ca 2+ homeostasis and systolic function and suggest Gα o may be an effective therapeutic target for the treatment of heart failure.

Although high thromboembolic risk was assumed in elderly patients with heart failure (HF) and atrial fibrillation (AF), inadequate control of prothrombin time/international normalized ratio was often observed in patients using vitamin K antagonists (VKAs). We hypothesized that patients treated with direct oral anticoagulants (DOAC) would have a better outcome than those treated with VKAs. The aim of this study was to compare the efficacies of DOACs and VKAs in elderly patients with HF and AF. We retrospectively analyzed data from a multicenter, prospective observational cohort study. A total of 1036 patients who were hospitalized for acute decompensated HF were enrolled. We assessed 329 patients aged > 65 years who had non-valvular AF and divided them into 2 groups according to the anticoagulant therapy they received. A subgroup analysis was performed using renal dysfunction based on estimated glomerular filtration rate (eGFR; mL/min/1.73 m2). The primary outcome was all-cause mortality, and the secondary outcomes were non-cardiovascular death or stroke. The median follow-up period was 730 days (range 334–1194 days). The primary outcome was observed in 84 patients; non-cardiovascular death, in 25 patients; and stroke, in 14 patients. The Kaplan–Meier analysis revealed that all-cause mortality was significantly lower in the DOAC group than in the VKA group (log-rank p = 0.033), whereas the incidence rates of non-cardiovascular death (log-rank p = 0.171) and stroke (log-rank p = 0.703) were not significantly different in the crude population. DOAC therapy was not associated with lower mortality in the crude population (log-rank p = 0.146) and in the eGFR ≥ 45 mL/min/1.73 m2 subgroup (log-rank p = 0.580). However, DOAC therapy was independently associated with lower mortality after adjustments for age, diabetes mellitus, and albumin level (hazard ratio, 0.55; 95% confidence interval, 0.30–0.99; p = 0.045) in the eGFR 2 subgroup. Compared with VKA therapy, DOAC therapy was associated with lower risk of all-cause mortality in the elderly HF patients with AF and renal dysfunction.

Purpose: Information on the relationship between frailty and the outcome of endovascular therapy (EVT) in elderly patients with lower extremity peripheral artery disease (PAD) is scarce. This study aimed to reveal the impact of frailty on the prognosis of super-elderly patients who underwent EVT. Materials and Methods: From August 2015 to August 2016, 335 consecutive patients who underwent EVT were enrolled in the I-PAD registry from 7 institutes in Nagano prefecture. Among them, we categorized 323 patients into 4 groups according to age and the presence or absence of frailty as follows: elderly with frailty (age ≥ 75, Clinical Frailty Scale [CFS] ≥ 5), elderly without frailty (age ≥ 75, CFS ≤ 4), young with frailty (age < 75, CFS ≥ 5), and young without frailty (age < 75, CFS ≤ 4); we analyzed them accordingly. The primary endpoints were major adverse cardiovascular and limb events (MACLE), defined as a composite of cardiovascular death, myocardial infarction, stroke, admission for heart failure, major amputation, and revascularization. The secondary endpoint was cardiovascular death. Results: The median follow-up period was 2.7 years. In the elderly with frailty, elderly without frailty, young with frailty, and young without frailty groups, the freedom rates from MACLE were 34.9%, 55.7%, 35.4%, and 63.0%, respectively (pConclusion: Frailty as defined by CFS might be a predictor of MACLE incidence in patients with PAD who underwent EVT. By considering treatment indications for patients with PAD by focusing on frailty rather than age, we may examine whether EVT policies are appropriate and manage patient and caregiver expectations for potential improvement in functional outcomes. Further studies are expected to investigate whether changes in frailty after EVT change prognosis.

The Reiwa First Year East Japan Typhoon of 2019 caused a torrential flood in Japan. In Nagano City, a large area was flooded due to the collapse of the Chikuma River embankment. After large-scale disasters, an increase in cardiovascular and cerebrovascular events has been reported on account of the stressful conditions. However, few reports of disaster-related diseases associated with flood damage have been described. Thus, our aim was to elucidate the effect of floods on the incidences of cardiovascular and cerebrovascular diseases in Nagano City.The Shinshu Assessment of Flood Disaster Cardiovascular Events (SAVE) trial enrolled 2,426 patients admitted for cardiovascular or cerebrovascular diseases at all five hospitals with an emergency department in Nagano City from October 1 to December 31 in the years 2017, 2018, and 2019. The occurrence of these diseases was calculated in every 2 weeks and the findings of 2019 (year of the flood) were compared with those of 2017 and 2018.Cardiovascular and cerebrovascular diseases significantly increased during the 2 weeks immediately after the flood disaster (149 in 2019 vs average of 116.5 in the previous 2 years, p 0.05). Unstable angina cases significantly increased 1.5-2 months after the flood disaster, and cerebral hemorrhage cases significantly increased in the 2 weeks after the flood disaster.Cardiovascular and cerebrovascular events increased significantly during the 2 weeks immediately after the large-scale flood disaster caused by the Reiwa First Year East Japan typhoon. Because of the increasing frequency of flood disasters, it is necessary to predict the occurrences of cardiovascular and cerebrovascular diseases and to implement guidelines for their appropriate and timely management.

The Glasgow Prognostic Score (GPS) has been established as a useful resource to evaluate inflammation and malnutrition and predict prognosis in several cancers. However, its prognostic significance in patients with heart failure (HF) is not well established. To investigate the association between the GPS and mortality in patients with HF, we assessed 870 patients who were 20 years old and more and had been admitted for acute decompensated HF. The GPS ranged from 0 to 2 points as previously reported. Over the 18-month follow-up (follow-up rate, 83.9%), 143 patients died. Increasing GPS was associated with higher HF severity assessed by New York Heart Association functional class and B-type natriuretic peptide (BNP) levels. Kaplan–Meier analysis showed significant associations for mortality and increased GPS. In multivariate analysis, compared to the GPS 0 group, the GPS 2 group was associated with high mortality (hazard ratio 2.92, 95% confidence interval 1.77–4.81, p

An inverse correlation between body mass index and mortality in patients with peripheral artery disease (PAD) has been reported. However, little information is available regarding the impact of body composition on the clinical outcomes in patients with PAD. This study evaluated the relationships between the lean body mass index (LBMI), body fat % (BF%), and mortality and major amputation rate in patients with PAD. We evaluated 320 patients with PAD after endovascular treatment (EVT) enrolled from August 2015 to July 2016 and divided them into low and high LBMI and BF% groups based on their median values (17.47 kg/m2and 22.07%, respectively). We assessed 3-year mortality and major amputation for the following patient groups: Low LBMI/Low BF%, Low LBMI/High BF%, High LBMI/Low BF%, and High LBMI/High BF%. During the median 3.1-year follow-up period, 70 (21.9%) patients died and 9 (2.9%) patients experienced major amputation. The survival rate was lower in the Low LBMI than in the High LBMI group, and was not significantly different between the Low and High BF% groups. Survival rates were lowest in the Low LBMI/Low BF% group (57.5%) and highest in the High LBMI/High BF% group (94.4%). There were no significant differences in major amputation rate between the Low LBMI and High LBMI groups, and between the Low BF% and High BF% groups. The Low LBMI and Low BF% groups were associated with an increased risk of mortality after adjustment for age, sex, frailty and conventional risk factors [hazard ratio (HR): 4.02; 95% confidence interval (CI) 2.10–7.70;p p = 0.005, respectively], for age, sex, hemodialysis, and prior cerebral cardiovascular disease (HR: 3.63; 95% CI 1.93–6.82;p p = 0.009, respectively) and for age, sex, and laboratory date (HR: 3.97; 95% CI 1.88–8.37;p p = 0.026, respectively). In conclusion, Low LBMI and Low BF% were associated with poor prognosis in patients undergoing EVT for PAD, and mortality was the lowest in the High LBMI/High BF% group compared with other body composition groups.

Background Understanding patient journey and burden of disease in patients with chronic thromboembolic pulmonary hypertension (CTEPH) helps improve diagnostic and treatment processes. Objectives This study aimed to explore patient journey from time of disease onset to a definitive diagnosis and disease burden in Japanese patients with CTEPH. Methods A mixed-methods study exploring patient journey and disease burden of 33 Japanese patients with a definitive diagnosis of CTEPH. The patients from 2 university hospitals underwent semistructured interviews. Data were transcribed into verbatim records, and 2 independent researchers conducted thematic analyses. Data concerning patient journey were also analyzed quantitatively with supplementary use of medical records. Results Median times from initial onset of symptoms to a confirmed diagnosis and first visitation to a medical institution to a definitive diagnosis of CTEPH were 32 and 20 months, respectively. Thematic analyses found that, for patients, reasons for delay in seeking initial consultations included misattribution of symptoms to aging or lack of physical strength. For healthcare providers, reasons for delays in diagnosis included poor recognition of CTEPH and difficulty in recalling the disease as a differential diagnosis. Burdens of CTEPH were caused by physical symptoms, and mental and social issues, including restriction of daily activities owing to oxygen therapy, disappointment with the intractable nature of the disease, poor understanding of the disease by other people, and lack of social networks. Conclusions This study highlighted physical, mental, and social burdens in patients with CTEPH and possible missed opportunities in making the diagnosis of CTEPH during the patient journey. Increasing disease awareness in healthcare providers and networking among patients may contribute to better patient care.

In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old.This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed.A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase.Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.

The incidence of Dressler’s syndrome after myocardial infarction (MI) has decreased in the reperfusion therapy era. Although guidelines recommend high-dose aspirin for treatment based on evidence from the pre-percutaneous coronary intervention (pre-PCI) era, bleeding and thrombotic concerns occurred upon aspirin administration after coronary stenting. A 69-year-old man with recent MI was admitted to our hospital. The patient presented with chest pain 1 week before admission. Electrocardiography revealed newly detected atrial fibrillation with no ST segment change. Urgent coronary angiography demonstrated a left circumflex artery occlusion. He underwent PCI, and a sirolimus-eluting stent was deployed. Aspirin, prasugrel, and apixaban were administered. However, hospital discharge was delayed because he developed heart failure during hospitalization. Twenty-three days after admission, he developed a fever of >39 °C. Electrocardiography showed anterior ST segment elevation, and echocardiography revealed a 6-mm pericardial effusion. We diagnosed the patient with Dressler’s syndrome, and colchicine 0.5 mg/day + acetaminophen 2000 mg/day were administered. His condition clinically improved after treatment and he was discharged 32 days after admission. There was hesitation about administration of high-dose aspirin in a patient who has undergone recent coronary stenting. Combination therapy of colchicine and acetaminophen could be a treatment option for Dressler’s syndrome.

Transvenous lead extraction (TLE) is an established procedure for the management of cardiovascular implantable electronic devices. However, some difficulties and risks of complications still exist, especially in old and adhered leads. Evolution RL (Cook Medical, Bloomington, IN, USA) is a newly introduced device for TLE; however, no clinical results have been reported in Japan, and the results with older leads are unknown. We investigated the efficacy and safety of Evolution RL and its usefulness for old leads at two TLE centers in Japan.A total of 27 consecutive patients who underwent lead extraction using Evolution RL at Shinshu University Hospital and Tokyo Women's Medical University Hospital from September 2017 to December 2019 were retrospectively enrolled. We examined the backgrounds of the patients and leads and investigated the efficacy and safety of the procedures. We divided the leads into two groups according to the number of years of implantation (10 years) and compared the results.Among the 27 patients, 20 (74.1%) were men, and the median age was 62 (14-91) years. The total number of leads was 58, and the median implantation duration was 136 months (8-448). We achieved clinical success in all patients and complete procedural success in 24 patients (88.9%). In three patients, the broken tip of the lead remained in the heart. No major complications were noted. Of the 58 leads, there were 34 leads with more than 10 years of implantation, with significantly more Evolution RLs used (94.1% vs. 54.2%, p = 0.001) and significantly higher percentages of Evolution 11Fr, 13Fr, and steady sheaths used (79.4% vs. 33.3%, p = 0.001, 52.9% vs. 16.7%, p = 0.006, and 64.7% vs. 20.8%, p = 0.001, respectively).In two TLE centers in Japan, Evolution RL was shown to be safe and effective, even in leads older than 10 years.

Aims A sodium glucose cotransporter 2 (SGLT2) inhibitor was recently found to reduce heart failure hospitalization in the EMPA‐REG OUTCOME trial. We have hypothesized that autonomic nerve activity may be modulated by SGLT2 inhibition. The current study aims to investigate the impact of empagliflozin on sympathetic and parasympathetic nerve activity in patients with type 2 diabetes mellitus. Methods and results This ongoing study is a prospective, randomized, open‐label, multicentre investigation of 134 patients with type 2 diabetes mellitus. The patients are randomly allocated to receive either empagliflozin or sitagliptin with the treatment goal of the Japan Diabetes Society guidelines. Ambulatory electrocardiographic monitoring is performed at the baseline and at 12 and 24 weeks of treatment. Analyses of heart rate variability are conducted using the MemCalc method, which is a combination of the maximum entropy method for spectral analysis and the non‐linear least squares method for square analysis. The primary endpoint is the change in the low‐frequency (0.04–0.15 Hz)/high‐frequency (0.15–0.4 Hz) ratio from baseline to 24 weeks. Conclusions This investigation on the effect of EMPagliflozin on cardiac sYmpathetic and parasympathetic neRve activity in JapanEse pAtieNts with type 2 diabetes (EMPYREAN study) offers an important opportunity to understand the impact of SGLT2 inhibition on autonomic nerve activity in patients with type 2 diabetes.

Aims This study aims to investigate the prognostic impact of mineralocorticoid receptor antagonists (MRAs) on cardiovascular events in patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF; defined as left ventricular ejection fraction ≥45%). Methods and results A prospective multicentre cohort study was conducted in Nagano prefecture, Japan, between July 2014 and December 2018 that contained 518 consecutive HFpEF patients hospitalized for acute decompensated heart failure (HF). The primary outcome was a composite of cardiovascular death and HF readmission. We compared the incidence of cardiovascular events between patients who were prescribed with MRAs and those who were not in a propensity score matched cohort using a Cox proportional hazards regression model with a propensity score derived from 23 baseline variables. For sensitivity analysis, we conducted Cox proportional hazards regression models for the primary outcome adjusting for 16 clinically relevant variables in the crude cohort. The median age was 83 years, and 53% were female. The median left ventricular ejection fraction was 61%. During a median follow‐up of 553 days, the primary outcome occurred in 192 (37%) patients. MRAs were used in 255 (49%) patients. After analysis, a matched cohort consisting of 370 patients was created. After propensity score matching, the baseline characteristics were well balanced between the two groups. The incidence of the primary outcome was significantly lower in MRA users than in non‐users [32% (59/185) vs. 49% (90/185); hazard ratio (HR) 0.669, 95% confidence interval (CI) 0.482–0.929, P = 0.016]. The incidence of cardiovascular death was also significantly lower in the MRA users [11% (21/185) vs. 22% (41/185); HR, 0.563; 95% CI, 0.333–0.953; P = 0.032]. The risk of HF readmission tended to be lower in the MRA users [29% (54/185) vs. 41% (75/185); HR, 0.738; 95% CI, 0.520–1.048; P = 0.089]. MRA use was also associated with a lower risk of the primary outcome after Cox proportional hazards analysis adjusting for 16 clinically relevant variables in the crude cohort (HR, 0.710; 95% CI 0.507–0.995; P = 0.047). Conclusions Mineralocorticoid receptor antagonist use was significantly associated with a lower risk of the primary composite outcome of cardiovascular death and HF readmission in patients hospitalized for acute decompensated HFpEF. The incidence of cardiovascular mortality was also significantly lower in these patients.

This study aimed to evaluate the early vascular response of ultra-thin strut bioresorbable polymer sirolimus-eluting stents (BP SES) using optical frequency domain imaging (OFDI). Ultra-thin strut BP SES have superior outcomes in terms of efficacy and safety endpoints when compared to other thin strut new-generation stents. However, the factors contributing to the superiority of BP SES over other thin strut new-generation stents are unclear. A total of 32 patients with multivessel disease requiring staged procedures at 1 month were enrolled from 3 cardiovascular institutions; of these, 31 were immediately assessed by OFDI (n = 31). All patients were assessed at 1 month after ultra-thin strut BP SES implantation. The primary endpoint was % of uncovered struts. A total of 1723 cross sections (17,014 struts) were analyzed at baseline and 1 month after percutaneous coronary intervention. The % uncovered struts at 1-month follow-up was 7.7% (4.0, 13.8). Furthermore, the covered strut % (88.4% and 80.4%, P = 0.013) and malapposition rate (2.7% and 4.3%, P = 0.012) were significantly different between the 60-μm and 80-μm stents. Ultra-thin strut BP SES implantation may feasibly achieve early vascular responses due to the ultra-thin struts. This may ultimately lead to lower stent thrombosis and target lesion failure rates. Clinical trial registration University Hospital Medical Information Network Clinical Trials Registry (No. UMIN000033406).

Nutritional status is a novel approach to prognostic assessment in patients with cardiovascular disease. However, assessment of nutritional status in elderly patients is challenging due to the significant differences between young patients. The TCBI (Triglycerides × Total cholesterol × Body Weight Index) is a novel and simple nutritional index for predicting long-term outcomes in patients with coronary artery disease. This retrospective study evaluated the efficacy of TCBI in 597 elderly (≥ 75 years) patients enrolled in the SHINANO 5 year registry. The SHINANO 5 year registry, a prospective observational multicenter cohort study, had enrolled 1501 consecutive patients who underwent elective/urgent percutaneous coronary intervention (PCI). In this study, patients were categorized into TCBI quartile groups. The primary endpoints were the occurrence of major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, stroke, and myocardial infarction at 5 year. The mean duration of follow up was 4.3 ± 1.7 years. The average patient age was 80.9 ± 4.3 years. MACCE was observed in 61 (40.9%) patients in the lowest TCBI quartile group. Kaplan–Meier analysis demonstrated an inverse relationship between MACCE and TCBI (log-lank P

Little is known about the impact of changes in body mass index (BMI) after the percutaneous coronary intervention (PCI) on long-term outcomes in patients with coronary artery disease (CAD). Therefore, this study aimed to clarify this issue. We investigated data on CAD obtained from the SHINANO Registry, a prospective, observational, multicenter cohort study, from 2012 to 2013 in Nagano, Japan. One year after PCI, the enrolled patients were divided into the following three groups based on changes in BMI by tertiles: reduced, maintained, and elevated BMI. The associations among the groups and the 4-year outcomes [major adverse cardiac events (MACEs), all-cause death, Q-wave myocardial infarction, and stroke] were examined. Five hundred seventy-two patients were divided into the reduced, maintained, and elevated BMI groups. Over the 4-year follow-up period, the cumulative incidence of MACEs was 10.5% (60 cases). In the Kaplan–Meier analysis, the incidence rates of MACE were significantly higher in the reduced BMI group than in the maintained and elevated BMI groups [17.7% versus (vs.) 7.3% vs. 9.0%, p = 0.004]. Multivariable cox regression analysis showed that the reduced group showed increased risks of MACEs (hazard ratio 2.15; 95% confidence interval 1.29–3.57; p = 0.003). The long-term clinical outcomes of patients with CAD who underwent PCI were affected by the reduction in BMI after PCI. Furthermore, the elevation of BMI after PCI was not a poor prognostic factor.

Prediction of short-term mortality in elderly patients with heart failure (HF) would be useful for clinicians when discussing HF management or palliative care.A prospective multicenter cohort study was conducted between July 2014 and July 2018. A total of 504 consecutive elderly patients (age ≥ 75 years) with HF (mean age 85 years, 50% women) were enrolled. We used a multiple logistic regression analysis with stepwise variable selection to select predictive variables and to determine weighted point scores. After analysis, the following variables predicted short-term mortality and comprised the risk score: previous HF admission (3 points), New York Heart Association III or IV (2 points), body mass index < 17.7 kg/m2 (4 points), serum albumin < 3.5 g/dL (9 points), and left ventricular ejection fraction < 50% (2 points). The c-statistic was 0.820. We compared mortality in low-risk (0-6 points, n = 188), intermediate-risk (7-13 points, n = 241), and high-risk (14-20 points, n = 75) groups. A total of 43 (8.5%) patients died within 6 months after discharge. Mortality was significantly higher in groups with higher scores (low-risk group, 0.5%; intermediate-risk group, 9.1%; high-risk group, 26.7%; P < 0.001).We developed a predictive model for 6-month mortality in elderly patients with HF. This risk score could be useful when discussing advanced HF therapies, palliative care, or hospice referral with patients.

The prognostic significance of resting heart rate (HR) in atrial fibrillation (AF) patients with heart failure with reduced ejection fraction (HFrEF) is unclear, and there are no recommendations about the optimal HR in patients with HF in the current guidelines. Thus, we aimed to identify the relationship between resting HR and mortality in AF patients with HFrEF. A prospective multicenter cohort study was conducted between July 2014 and December 2018. We enrolled consecutive 144 AF patients with HFrEF (mean age 75 years, 34% female). The primary endpoint was all-cause death. We compared the outcomes between the high HR group (HR81 beats per minute [bpm], interquartile range [IQR] of HR ≥ 67%, n = 50), and the low HR group (HR ≤ 81 bpm, IQR of HR67%, n = 94). During a median follow-up of 538 days, the primary endpoint occurred in 41 (28.5%) patients. In Kaplan-Meier analysis, high HR was associated with a progressively increased risk of mortality (log-rank test, p = 0.034). After multivariate Cox regression analysis, high HR predicted all-cause death after adjusting for age, sex, hemoglobin, estimated glomerular filtration rate, LVEF, use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, digoxin, amiodarone, and calcium channel blockers (hazard ratio, 1.979; 95% confidence interval, 1.005-3.898; p = 0.048). Resting HR81 bpm at discharge had a significantly higher risk of death compared with HR ≤ 81 bpm in AF patients with HFrEF.

We investigated the prognostic effects of hyperuricemia and high or low body mass index (BMI) in peripheral artery disease (PAD) after endovascular therapy (EVT). Between July 2015–2016, 357 consecutive patients with PAD who underwent EVT were enrolled. Patients were divided into 2 groups: BMI < 25 kg/m2 (low BMI) and ≥ 25 kg/m2 (high BMI); they were also divided into 2 more groups based on the presence/absence of hyperuricemia. The primary and secondary endpoints were major adverse cardiovascular and limb events (MACLE), and all-cause death at 3 years post-EVT. Patients with hyperuricemia had significantly lower freedom from MACLE than patients without hyperuricemia at 3 years (57.0 vs 71.9%, p = .0068). The overall survival of patients with hyperuricemia was significantly lower than that of patients without hyperuricemia (63.9 vs 81.7%, p = .0012). Patients with hyperuricemia who had low BMI experienced significantly lower freedom from MACLE than those without hyperuricemia who had low BMI (48.2 vs 69.9%, p = .002). The overall survival of patients with hyperuricemia who had low BMI was significantly lower than that of patients without hyperuricemia who had low BMI (55.2 vs 77.1%, p = .003). Patients with hyperuricemia had significantly more MACLE and a lower survival at 3 years than patients without hyperuricemia, even if they had a low BMI.

BACKGROUND: Polypharmacy is a common problem among patients with acute decompensated heart failure (ADHF) who often have multiple comorbidities. OBJECTIVE: The aim of this study was to define the number of medications at hospital discharge and whether it is associated with clinical outcomes at 1 year. METHODS: We evaluated the number of medications in 2578 patients with ADHF who were ambulatory at hospital discharge in the Kyoto Congestive Heart Failure Registry and compared 1-year outcomes in 4 groups categorized by quartiles of the number of medications (quartile 1, ≤ 5; quartile 2, 6-8; quartile 3, 9-11; and quartile 4, ≥ 12). RESULTS: At hospital discharge, the median number of medications was 8 (interquartile range, 6-11) with 81.5% and 27.8% taking more than 5 and more than 10 medications, respectively. The cumulative 1-year incidence of a composite of death or rehospitalization (primary outcome measure) increased incrementally with an increasing number of medications (quartile 1, 30.8%; quartile 2, 31.6%; quartile 3, 39.7%; quartile 4, 50.3%; P < .0001). After adjusting for confounders, the excess risks of quartile 4 relative to those of quartile 1 remained significant (P = .01). CONCLUSIONS: In the contemporary cohort of patients with ADHF in Japan, polypharmacy at hospital discharge was common, and excessive polypharmacy was associated with a higher risk of mortality and rehospitalizations within a 1-year period. Collaborative disease management programs that include a careful review of medication lists and an appropriate deprescribing protocol should be implemented for these patients.

Acute lymphocytic myocarditis in pregnancy is rare, with no established management guidelines to date. A 40-year-old woman at 34 weeks of gestation complained of shortness of breath upon exertion. An electrocardiogram revealed broad ST elevation, and echocardiography showed diffuse impairment of left ventricular contractility. The patient was immediately transferred to our hospital for suspected takotsubo cardiomyopathy. We considered myocarditis based on the patient’s prior cold-like symptoms and additional examination. Myocardial biopsy revealed lymphocyte infiltration, which confirmed acute lymphocytic myocarditis. Although there were no signs of heart failure or conduction disturbance under catecholamine, her hemodynamics were weak. Emergency cesarean section was performed because of possible hemodynamic failure during the remaining course of pregnancy. Both the mother and baby were discharged without any subsequent events. If acute myocarditis is suspected during pregnancy, prompt myocardial biopsy is crucial for timely pathological diagnosis and treatment decisions. Clinicians should consider premature delivery prior to a possible failure in maternal hemodynamics.

During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however.We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant.We found that cardiac expression of GαThese findings shed light on a novel function of Gα

Background Polypharmacy would be associated with poor prognosis in patients with heart failure (HF). Methods In 863 patients who discharged after treatment for HF were prospectively enrolled. Number of tablets prescribed at discharge was counted. Death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF were tracked. Results In our study cohort (median age, 78), 447 patients experienced adverse events during median 503 days follow-up. In Kaplan-Meier analysis, a greater number of prescribed tablets was associated with future adverse cardiac events in the crude population. Although patients with the greater number of non-HF medications showed worse outcome, those of HF medications were not associate with the outcome (Figure). Furthermore, the number of tablets was an independent predictor of future cardiovascular events after adjustment for age, gender, B-type natriuretic peptide, hemoglobin, albumin, estimated glomerular filtration rate, and left ventricular ejection fraction (HR 95% CI: 1.295 (1.066–1.573), p=0.009). Conclusions Polypharmacy was associated with poor prognosis. Although the numbers of tablets and non-HF medications were significantly associated with worse out come in HF patients, the number of HF medications was not. Funding Acknowledgement Type of funding sources: None.

Background Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.

Heart failure with preserved ejection fraction (HFpEF) has currently become a major concern in the aging society owing to its substantial and growing prevalence. Recent investigations regarding sacubitril/valsartan have suggested that there is a gender difference in the efficacy of the medication in HFpEF cohort. However, information of gender difference in clinical profiles, examination, and prognosis have not been well investigated. The present study aimed to evaluate the differences in baseline characteristics and outcomes between women and men in a Japanese HFpEF cohort. We analyzed the data from our prospective, observational, and multicenter cohort study. Overall, 1036 consecutive patients hospitalized for acute decompensated heart failure were enrolled. We defined patients with an ejection fraction (EF) of ≥ 50% as HFpEF. Patients with severe valvular disease were excluded; the remaining 379 patients (women: n = 201, men: n = 178) were assessed. Women were older than men [median: 85 (79–89) years vs. 83 (75–87) years, p = 0.013]. Diabetes mellitus, hyperuricemia, and coronary artery disease were more prevalent in men than in women (34.8% vs. 23.9%, p = 0.019, 23.6% vs. 11.4%, p = 0.002, and 23.0% vs. 11.9%, p = 0.005, respectively). EF was not significantly different between women and men. The cumulative incidence of cardiovascular death or hospitalization for congestive heart failure (CHF) was significantly lower in women than in men (log-rank p = 0.040). Women with HFpEF were older and less often exhibited an ischemic etiology; further, they were associated with a lower risk for cardiovascular death or hospitalization for CHF compared with men in the Japanese population.

An 80-year-old man with a history of dilated hypertrophic cardiomyopathy received a dual-chamber pacemaker for sick sinus syndrome and atrioventricular block in February 2010. On May 30, 2019, he developed pocket erosion, with streaks of pus exuding from the pocket. The pacemaker generator was removed, although both capping leads were left buried under the skin, and a leadless pacemaker was implanted into the right ventricular (RV) apex the next day. Blood and pus cultures on July 15, 2019 indicated methicillin-resistant Staphylococcus aureus (MRSA). The patient was transferred to our hospital for simultaneous removal of both devices in August 2019. The RV lead and right atrial lead were extracted using a laser sheath and a mechanical sheath. A 23 Fr MICRA® sheath was inserted from the right femoral vein to accommodate an 8.5 Fr Agillis sheath. An Osypka LASSO snare catheter was advanced through the sheath to catch the distal aspect of the MICRA® body. Finally, the MICRA® device was completely removed through the sheath. Culture results for the lead tip and MICRA® were both MRSA positive. This is the first report of late-phase simultaneous infection of abandoned leads and implanted leadless cardiac pacemaker extraction.

Significant improvements in percutaneous coronary intervention (PCI) technology have enabled cardiovascular procedures to be performed without onsite cardiac surgery facilities. However, little is known about the association between onsite cardiac surgical support and long-term outcomes of PCI, particularly among emergent and complex cases. We investigated whether the presence or absence of cardiovascular surgery affects the long-term prognosis after PCI, emergent and complex elective cases. The SHINANO 5-year registry, a prospective, observational, and multicenter cohort study registry in Nagano, Japan, consecutively included 1665 patients who underwent PCI between August 2012 and July 2013. The procedures were performed at 11 hospitals with onsite cardiac surgery facilities [onsite surgery (+) group; n = 1257] and 8 hospitals without onsite cardiac surgery facilities [onsite surgery (−) group; n = 408]. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiac and cerebrovascular events [MACCE: all-cause death, Q-wave myocardial infarction, non-fatal stroke, and target lesion revascularization]. The onsite surgery group (+) had a lower rate of emergent PCI and ST-segment elevation myocardial infarction (40.8% vs. 51.7%, p p p p p = 0.421) and MACCE incidence (31.6% vs. 28.9%, p = 0.354) between the groups. Also, there were no differences in the mortality rate and incidence of MACCE among emergent cases of ST-segment elevation myocardial infarction and complex elective cases who underwent PCI. Long-term outcomes of PCI appear to be comparable between institutions with and without onsite cardiac surgical facilities.

BackgroundTreatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH.MethodsIn this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide.ResultsThe change in PVR was −98.2±111.3 dyn·s·cm−5 and −4.6±163.6 dyn·s·cm−5 in the selexipag and placebo groups, respectively (mean difference −93.5 dyn·s·cm−5; 95% CI −156.8 to −30.3; p=0.006). The changes in cardiac index (pConclusionSelexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.